Adoption of the FDA’s Process Analytical Technology (PAT) guidance and implementation of PAT throughout the pharma/biotech industry on the small molecule side has been quite good, “but progress in large molecular development has been much slower,” says Rick Cooley, manager of the process analytics center of excellence at Dionex (www.dionex.com). Cooley attributes this distinction primarily to the complexity of secondary, tertiary, and quaternary structures that complicate analysis and control strategies in the manufacturing of proteins and other large molecules.
In a sense, by accepting and encouraging the principles of PAT, the FDA “openly communicated to the industry that it recognizes it is part of the problem,” says Cooley. The FDA also recognizes the opportunities PAT has to offer, which are evident from the benefits achieved using PAT and other process optimization and efficiency strategies implemented in the past by, for example, the petrochemical industry.
Sandy Weinberg, senior director, fast-track biodefense, GE Healthcare (www.gehealthcare.com), anticipates that within three to five years more companies will be assessing where they are in terms of PAT, and he envisions the potential for dramatic changes in five to ten years.
The main challenge, Weinberg suggests, is how to apply process monitoring, “to go from looking at the product to looking at the process,” because improving the process will improve the product.
Ajaz Hussain, Ph.D., vp and global head of biopharmaceutical development, and former deputy director for science in the U.S. FDA’s Center for Drug Evaluation and Research, sees PAT as an important opportunity for the pharma/biotech industry.
“For biological processing, people have agreed that the process is the product,” says Dr. Hussain. “To some extent that is true, but unless you design your manufacturing process and control it effectively, you are locking your process in to 20-year-old technology.”
Historically, biopharma had a view of PAT as a sensor- or instrument-driven approach to process control with limited application to bioprocesses involving living organisms. However, PAT includes more than putting more sensors in a fermentation tank or process stream, explains Lou Bellafiore, president of TechniKrom (www.technikrom.com). It encompasses the implementation of manufacturing science to large-scale biological manufacturing and involves identifying and controlling sources of variability in these processes.
John Walker, vp of engineering at TechniKrom, emphasizes three key demands of PAT: “clear process understanding, competent instrumentation, and an appropriate control system that knows when and how to intervene to guarantee product quality.”